Polymyalgia rheumatica

What is polymyalgia rheumatica?

Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown cause which is characterised by severe bilateral pain and morning stiffness of the shoulder, neck and pelvic girdle. There is ongoing debate as to whether or not PMR represents a form of giant cell arteritis (GCA), or whether they are distinct conditions, as they often co-exist, they share many common features and both respond to corticosteroids.¹ 40-50% of people with GCA have associated PMR, and around 30% of those with PMR go on to develop GCA.²

How common is polymyalgia rheumatica? (Epidemiology)³

• The annual incidence of the disease in the general population in the UK has been estimated as 95 per 100,000.

• Globally, the incidence is thought to be between 58 to 96 per 100,000.¹

• PMR occurs almost exclusively in people aged above 50 and the mean age of onset is about 73.⁴

• Lifetime risk is around 2.4% for women and 1.7% for men.⁵

• PMR is seen mainly in people of north European ancestry, although it can occur in any ethnic group.

Causes of polymyalgia rheumatica (aetiology)¹

The cause of PMR is unknown. Studies suggest that both genetic and environmental factors might be important in disease pathogenesis.

Familial aggregation is has been described. Genetic studies have shown the presence of the HLA-DRB1*04 allele in up to 67% of cases of PMR.¹

There have also been studies showing a possible association between PMR and diverticulitis, suggesting a possible role of the microbiome in polymyalgia rheumatica development.¹

Some studies have suggested an infectious aetiology hypothesis with clustering of PMR and GCA during epidemics of mycoplasma pneumonia and parvovirus. However, other studies have not supported these hypotheses.¹

Polymyalgia rheumatica symptoms (presentation)¹²⁶

The presenting symptoms tend to be symmetrical pain and stiffness in and around the shoulders, neck and hip girdle. The onset is often acute or semi-acute, usually arising within a few days although it can start overnight. Core inclusion criteria for a diagnosis of PMR include:

• Age over 50 years and duration of symptoms more than two weeks.

• Bilateral shoulder or pelvic girdle aching, or both.

• Morning stiffness of more than 45 minutes in duration.

• Evidence of an acute-phase response (raised ESR/CRP). The ESR varies from moderate to high (>100) with around 20% of patients having an ESR of <40 mm per hr. The CRP is more reliable and it is now thought that normal CRP levels are incompatible with a diagnosis of PMR.²

• PMR has however occasionally been diagnosed with a normal ESR and/or CRP where there was a classic clinical picture and response to steroids. All these patients should be referred for specialist assessment and management; diagnosis of PMR with normal CRP should not be made in general practice.

The most characteristic presenting feature of PMR is bilateral shoulder pain and stiffness of acute or subacute onset with bilateral upper arm tenderness. Symptoms are at their worst on waking. The stiffness may make it difficult to get out of bed, or raise their arms sufficiently to brush their hair. There may be flu-like features at the onset, which is usually sudden, or over the course of 1-2 weeks.

Exclusion criteria are active infection, cancer or GCA. Assessment should be made clinically for GCA, as this would require an immediate high-dose steroid and same-day referral, whereas a diagnosis of PMR can await further investigation, and the dose of steroid will be lower. Examination should be made to exclude other differential diagnoses as well as GCA, particularly looking for lymphadenopathy (there should be none for a diagnosis of PMR), thyroid disease or involvement of other organs and systems.

Differential diagnosis³

Inflammatory disorders

• Rheumatoid arthritis (RA).

• Late-onset spondyloarthropathy, including ankylosing spondylitis, psoriatic arthritis.

• Systemic lupus erythematosus, scleroderma, Sjögren's syndrome, vasculitis.

• Dermatomyositis, polymyositis.

Non-inflammatory disorders

• Degenerative disease: osteoarthritis, spinal spondylosis.

• Rotator cuff disease, adhesive capsulitis (frozen shoulder).

• Drug-induced myalgia (eg, statins).

• Infections, including viral syndromes, osteomyelitis, infective endocarditis, tuberculosis.

• Malignancy - eg, lymphoma, leukaemia, lung cancer, myeloma, prostatic carcinoma.

• Amyloidosis.

• Parkinsonism.

• Chronic pain syndromes, fibromyalgia, depression.

• Endocrinopathy and metabolic bone disease: hyperthyroidism, hypothyroidism, hyperparathyroidism, hypoparathyroidism, osteomalacia, pseudogout with calcium pyrophosphate deposition.
  

Investigations¹²⁶

Investigations are essential to support the diagnosis of PMR but also to rule out any other possible diagnosis. Investigations advised as essential by the British Society of Rheumatology (BSR) guidelines, to be done in all those with suspected PMR before starting steroid treatment, are:

• Inflammatory markers: ESR, plasma viscosity and/or CRP. Raised inflammatory markers are a characteristic laboratory finding in PMR but may be normal. CRP is more sensitive than ESR.

• FBC.

• U&Es.

• LFTs.

• Bone profile.

• Protein electrophoresis.

• TFTs.

• Creatine kinase.

• Rheumatoid factor.

• Urinalysis.

Further investigations to consider are:

• Urinary Bence Jones' protein.

• Autoantibodies - anti-nuclear antibody (ANA) and anti-cyclic citrullinated peptide (anti-CCP) antibody.

• CXR.

• Ultrasound scans of the shoulders and/or hips are sometimes used if the diagnosis is unclear. Typical findings on ultrasound include subdeltoid bursitis and biceps tendon tenosynovitis and, less frequently, synovitis of the glenohumeral joint or trochanteric bursitis.⁷⁸

Associated diseases

Consider GCA in all people with PMR. Symptoms of GCA include new headache, jaw claudication (jaw muscle pain on chewing) and visual disturbance. On examination, the temporal artery may be abnormal to palpation; biopsy of this artery usually yields characteristic findings of vascular inflammation. Such a biopsy should be considered in any patient with polymyalgic symptoms and new headache.

There may be some overlap with RA, and some people with PMR are subsequently diagnosed with RA. The presence of anti-CCP antibodies may alert the clinician to a diagnosis of early RA.

Treatment for polymyalgia rheumatica

Glucocorticoids are the only known effective treatment. Non-steroidal anti-inflammatory agents are of little value for the management of this disease. Typical starting dose is 15-25 mg daily of prednisolone.⁹The average duration of treatment is 1-2 years but 25% of patients require treatment for more than 4 years.⁹

PMR symptoms should respond dramatically to steroids. Even those with an incomplete response have significant benefit from glucocorticoids. Even those with an incomplete response reported a 70% reduction of symptoms.¹⁰

In practice, the response to glucocorticoids is incomplete in 29-45% of patients. More than 50% suffer from significant side effects. PMR is marked by relapses and the average relapse rate is 43% at one year.⁹Relapses should be managed by increasing the dose of prednisolone to the pre-relapse dose and reducing again after 4-8 weeks.

The evidence base for follow up is poor. Suggestions vary between following up every 1-4 weeks to every 1-4 months.⁹

There is evidence for the efficacy of steroid-sparing agents (eg, methotrexate or anti-tumour necrosis factor agents) particularly in those with a high risk of relapse and those with long-term glucocorticoid treatment. Methotrexate is the most commonly used corticosteroid sparing agent.⁹¹¹

There have been studies looking at the IL-6 pathway inhibitors, tocilizumab and sarilumab, in PMR. In the USA, sarilumab is now licensed for PMR for patients who are unable to take glucocorticoids or who cannot tolerate the steroid taper. They are not yet licensed in Europe or the UK.⁹

General points

• Manage any residual physical or psychosocial disability caused by the disease. Patients with PMR are frequently elderly and may have mobility problems and difficulty with many aspects of daily living. Some may benefit from referral to a physiotherapist and occupational therapist for assessment.

• Screen for increased risk of adverse reaction to steroids before starting (diabetes, hypertension, history of peptic ulcer, osteoporosis, mental health history).

• Unlike GCA, urgent institution of steroid therapy is not necessary and can be delayed to allow full assessment. However, if the patient does present with symptoms suspicious of GCA then urgent institution of high-dose steroid therapy is required.

• Lack of response to recommended doses of prednisolone, as well as atypical clinical features (younger age, muscle weakness, peripheral joint disease, and predominance of pain with little or no stiffness), should lead to consideration of alternative diagnoses.

• Patients should be assessed for response to an initial dose of prednisolone 15 mg daily orally. A patient-reported global improvement of at least 70% within a week of commencing steroids is consistent with PMR, with normalisation of inflammatory markers in four weeks. A lesser response should prompt the search for an alternative condition.

Recommended steroid therapy regime⁶

• Daily prednisolone 15 mg for three weeks.

• Then reduce to 12.5 mg for three weeks.

• Then reduce to 10 mg for four to six weeks.

• Then reduce by 1 mg every four to eight weeks or alternate day reductions (eg, 10/7.5 mg on alternate days).

• Tailor this to the individual according to symptoms.

• Treatment is usually required for one to two years. Maintenance dose is usually 2.5-5 mg daily. Steroids may be stopped when the patient is asymptomatic from their inflammatory symptoms.

Monitoring schedule³

Review the person after one to three weeks to assess clinical response to steroids and adverse effects. Also review one week after each dose change or at three-monthly intervals.

At each appointment, monitor response and review:

• Symptoms: morning stiffness, proximal hip and girdle pain, disability related to PMR. Symptoms and signs suggesting an alternative diagnosis.

• Ask about symptoms of GCA (headache, visual disturbance, jaw or tongue claudication.) Remind the person to present immediately if any of these symptoms develop.

• Adverse events including weight gain, dyspepsia, osteoporotic stress fractures.

• Check blood pressure.

• Laboratory markers: CRP and ESR and Hba1c.

Adverse effects of treatment:

• Glucocorticoid-related adverse events are common and include osteoporosis, avascular necrosis, infections, diabetes, insufficiency fractures, steroid myopathies, hypertension, hyperlipidaemia and cataracts.

• Drug-related side-effects include hyperlipidaemia and osteoporosis. These side-effects must be monitored and measures should be taken to prevent and manage them.

• Overtreatment with corticosteroids is often the result of underlying degenerative symptoms being misinterpreted as persistent PMR, or a persistently raised ESR being attributed to underlying active disease.

Prevention and treatment of steroid-induced osteoporosis⁶

See also the separate Osteoporosis risk assessment and primary prevention article.

• Individuals with high fracture risk - eg, aged 65 years or older or prior fragility fracture:

  • Bisphosphonate with calcium and vitamin D supplementation.

  • Dual-energy X-ray absorptiometry (DXA) scan is not required.

• Patients without high fracture risk:

  • Calcium and vitamin D supplementation when starting steroid therapy.

  • DXA scan is recommended. Bisphosphonates may be indicated if T score is 1.5 or lower.

• Individuals requiring higher initial steroid dose:

  • Bisphosphonate with calcium and vitamin D supplementation (higher cumulative steroid dose is likely).

Referral

Specialist referral is recommended for:

Atypical clinical presentations:

• Patient aged under 60 years.

• Chronic onset.

• Lack of shoulder involvement.

• Lack of inflammatory stiffness.

• 'Red flag' features: prominent systemic features, weight loss, night pain, neurological signs.

• Peripheral arthritis or other features of autoimmune or muscle disease.

• Normal or very high (ESR/CRP above 100) inflammatory markers.

Treatment dilemmas:

• Incomplete or non-response to corticosteroids.

• Ill-sustained response.

• Unable to reduce corticosteroid dose.

• Need for prolonged corticosteroid therapy (longer than two years).

• Contra-indications to corticosteroid therapy.

However, patients with a typical clinical picture and complete sustained response to treatment, and no adverse events, can be managed in primary care.

Relapse of disease⁶

Relapse is the recurrence of symptoms of PMR or onset of GCA, and not just unexplained raised ESR or CRP. Treatment of relapse:

• Clinical features of GCA: treat as GCA (usually oral prednisolone 40-60 mg daily). See the separate Giant cell arteritis article.

• Clinical features of PMR: increase prednisolone to previous higher dose.

• Further relapses: consider referring for immunosuppression therapy (eg, methotrexate) after two relapses.

Prognosis

• The risk of GCA occurring while PMR is being treated is approximately 30%.²

• The course and prognosis of PMR are very variable. Response to systemic corticosteroids is rapid and dramatic, usually within a few days, but treatment for 1-2 years is often required and some people may need low-dose corticosteroids for longer periods.

• Relapse is common but responds to restarting or increasing the dose of systemic corticosteroids.

• PMR is not associated with increased mortality but morbidity and mortality may occur as a result of immunosuppression or steroid side-effects.